Discovery Offers Promising Lead In Prostate Cancer Diagnosis

Researchers led by Dr. Shiv Srivastava from the Center for Prostate Disease Research (CPDR), Uniformed Services University of the Health Sciences (USU) in Maryland, report a groundbreaking discovery of the ETS Related Gene (ERG) as one of the most common proto-oncogene overexpressions in prostate cancer cells. This discovery provides a very promising addition to a select group of genes, whose expression is frequently altered in prostate cancer cells and have potential to improve diagnosis, prognosis or therapy of prostate cancer in the future.

The report by Dr. Gyorgy Petrovics et al on the discovery of the first major oncogenic alteration in early stage prostate cancer is published in the March 7 online issue of the leading cancer research journal Oncogene. Using laser capture microdissected prostate epithelial cells from malignant and benign prostate tissues and GeneChips, they identified the ERG gene as the first oncogene that is commonly overexpressed at the early phase of prostate cancer.

Oncogenes have long been known to be major factors in the development of cancer cells and mutation or altered expression of these genes, and have been identified in diverse human cancers. However, for prostate cancer, which is the most common non-skin cancer and the second leading cause of cancer-related deaths in men in the US, the identification of a higher frequency of oncogenic alterations have eluded scientists thus far.

This discovery was the result of a highly coordinated effort by urologists, pathologists and cancer biologists from the Walter Reed Army Medical Center (WRAMC), the USU, the Armed Forces Institute of Pathology (AFIP), the Walter Army Institute of Research (WRAIR) and the National Human Genome Research Institute (NIHGRI). The Henry M. Jackson Foundation for the Advancement of Military Medicine provides scientific and management services for this tri-service research program.

The CPDR researchers went on to assess the cancer association of ERG change in combination with other prostate cancer marker genes. They found that by combining ERG with two other genes, DD3 and AMACR, which are described by other laboratories as commonly overexpressed in prostate cancer, the three-gene panel exhibited cancer association in 98% of the prostate cancer patients tested, underscoring a promising potential in prostate cancer diagnosis. Intriguing correlations of ERG overexpression features have also been noted for PSA recurrence-free survival of prostate cancer patients after radical prostatectomy.

Oncogene inhibition or inactivation is one of the main strategies for cancer gene therapy. Due to the oncogenic nature of ERG, CPDR researchers are proposing the exploration of the ERG gene as a potential therapeutic target in prostate cancer treatment.